Patent GB-946578-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
Inventor: MAGERLEIN BARNEY JOHN
IPC: C07J5/00
Filed: 1960-12-19
Abstract: The invention comprises a compound having the general formula: <FORM:0946578/C2/1> wherein R represents hydroxy, -OPO3H2, -OSO2R11 wherein R11 is an alkyl or aryl radical or O Acyl, the term O Acyl representing the acyl radical of an organic carboxylic acid, R1 represents a b -hydroxy or keto group, Hal represents bromine, chlorine, fluorine or iodine and the 1,2-carbon atom linkage represents a single or double bond linkage providing that 1/. when R represents O Acyl and the 1,2-carbon linkage represents a single bond, R1 represents a keto group and 2/. when R represents -OPO3H2 or -OSO2R11, Hal represents fluorine, and a process for the preparation of compounds of the formula above the subjecting a compound of the formula: <FORM:0946578/C2/2> to oxidative hydroxylation and then if desired hydrolyzing and/or oxidizing to produce the corresponding free 21-hydroxy compound and 11-keto derivative; subsequently the 21-hydroxy compound may be treated with a alkyl or aryl sulphonyl halide to obtain a 21-OSO2R11 compound which may be treated with an alkali metal iodide to obtain a 21-iodo compound or silver dihydrogen phosphate to obtain a 21-OPO3H2 compound; treating the 21-OSO2R11 or the 21-iodo compound with a metal fluoride produces the 21-fluoro compounds. The oxidative hydroxylation may be effected using osmium tetroxide and an oxidizing agent e.g. hydrogen peroxide, an alkyl peroxide or an amine oxide peroxide. The starting compound is obtained by reacting a compound having the formula: <FORM:0946578/C2/3> wherein Ac is as defined above, with thionyl chloride or thionyl bromide to give a compound having the formula: <FORM:0946578/C2/4> and reacting the latter compound with a base in the presence of an inert solvent to produce a compound having the formula: <FORM:0946578/C2/5> reacting the latter compound with anhydrous hydrogen fluoride in the presence of an inert solvent to give a compound having the general formula: <FORM:0946578/C2/6> and then acylating to produce the corresponding 21-ester, A 1,2-double bond may be introduced into the D 4 compounds by microbiological fermentation e.g. with Septomyxa affinis. If the 16-halo compound used as starting material is a 16-chloro or 16-bromo compound it can be converted to the corresponding 16-fluoro compound by means of cadmium fluoride, potassium fluoride or lead fluoride or into the corresponding 16-iodo compound with sodium iodide.  The 16-fluoro-11b -hydroxy steroids may be dehydrated e.g. with N-bromoacetamide and anhydrous sulphur dioxide to obtain the corresponding D  9(11) compounds.  Specifications 850,833, 872,112, 873,219 and 946,579 also are referred to.ALSO:Pharmaceutical compositions having anti-inflammatory activity and comprising a compound of the general formula: p   <FORM:0946578/A5-A6/1> (wherein R represents hydroxy, -OPO3H2, -OSO2R11 wherein R11 is an alkyl or aryl radical, or OAc, the term Ac representing the acyl radical of an organic carboxylic acid, R1 represents a b -hydroxy or keto group, Hal represents bromine, chlorine, fluorine or iodine and the 1,2-carbon atom linkage represents a single or double bond linkage, providing that (1) when R represents OAc and the 1,2 linkage is a single bond, R1 represents a keto group, and (2) when R represents -OPO3H2 or -OSO2R11, Hal represents fluorine), with or without a coacting antibiotic, are administered orally in pills, tablets, capsules, syrups, or elixirs, in liquid forms for injection or topically as ointments, creams and lotions.